This application is for a NIDA P30 Center titled "Intersystem Regulation by Drugs of Abuse." We have evolved a strong group of funded investigators working on a variety of aspects of drug abuse and addiction. It has become apparent that a P30 Center would enhance the overall productivity, synergy, and integration of the interdisciplinary research and enable the recruitment of additional faculty into the field of drugs of abuse and addiction. The themes of the proposed Center are: 1) to determine the role of abused and therapeutically used opioids and the endogenous opioid system and its ligands, in regulation of pain, body temperature, the immune system, and infection, including HIV; 2) to determine the basic mechanisms responsible for these changes; 3) to compare effects produced by acutely administered drugs with those of chronically administered drugs. A corollary to these themes will be the determination of the similarities and differences in the mechanisms involved in these systems relative to the opioid and endogenous systems associated with abused drugs, and the relationships that exist among these systems relative to the opioid and endogenous systems associated with abused drugs, and the relationships that exist among these systems. In light of the fact that individuals rarely, if ever, abuse only one drug, it is particularly important to determine whether or not interactions occur between opioids and other abused drugs such as cocaine and marijuana. Both in vivo and in vitro approaches will be used, ranging form whole- animal measurements of behavior and activity, to biochemical and molecular techniques, to assess the overall mechanisms of action of opioids and other drugs of abuse in the brain and the periphery, and the feedback loops that integrate these systems. The potential for synergy among many investigators having diverse expertise and using multiple approaches and techniques is enormous. In order to carry out the aims of the Center, we are requesting 6 Cores: Administrative, Animal, Biochemical Pharmacology, Cell and Immunology, Integrative Pharmacology, and Molecular Biology. Members of the Center come from several departments, and have expertise in such areas as neuropharmacology, molecular pharmacology, quantitative and theoretical pharmacology, behavioral pharmacology, microbiology (bacteriology and virology), immunology, and biochemistry. Faculty from both basic science and clinical departments will be involved in the NIDA Center. A Center will be the glue that holds together and attracts others to this wide-ranging group of outstanding scientists. Temple University School of Medicine has made a major commitment in providing the funds and space necessary to form a Center. The NIDS Center will provide the Core facilities to foster the use of techniques and methods not currently available to the individual research. It will provide cost savings, and raise the quality of the science and the vision of future of research. It will truly provide the environment that will result in the highest quality, innovative, state-of-the-art research. It will provide what is necessary for our group to become a national resource in terms of several aspects of drug abuse research, especially drug interactions and neuroimmunopharmacology.